Intestinal Calcium Absorption Research Articles

A prospective study of vitamin D, proinflammatory cytokines, and risk of fragility fractures in women on aromatase inhibitors for breast cancer.

Vitamin D is critical to bone health by regulating intestinal absorption of calcium, whereas proinflammatory cytokines, including IL-1, IL-6, IL-12, and TNF-α, are known to increase bone resorption. We hypothesized that vitamin D and these cytokines at the time of breast cancer diagnosis were predictive for fragility fractures in women receiving aromatase inhibitors (AIs). In a prospective cohort of 1,709 breast cancer patients treated with AIs, we measured the levels of 25-hydroxyvitamin D (25OHD), IL-1β, IL-6, IL-12, and TNF-α from baseline blood samples. The associations of these biomarkers were analyzed with bone turnover markers (BALP and TRACP), bone regulatory markers (OPG and RANKL), bone mineral density (BMD) close to cancer diagnosis, and risk of fragility fractures during a median of 7.5 years of follow up. Compared to patients with vitamin D deficiency, patients with sufficient levels had higher bone turnover, lower BMD, and higher fracture risk; the latter became non-significant after controlling for covariates including BMD and no longer existed when patients taking vitamin D supplement or bisphosphonates or with history of fracture or osteoporosis were excluded. There was a non-significant trend of higher levels of IL-1β and TNF-α associated with higher risk of fracture (highest vs. lowest tertile, IL-1β: adjusted HR=1.37, 95% CI=0.94-1.99; TNF-α: adjusted HR=1.38, 95% CI=0.96-1.98). Our results do not support proinflammatory cytokines or vitamin D levels as predictors for risk of fragility fractures in women receiving AIs for breast cancer.

Diagnostic approach to rickets: an Endocrine Society of Bengal (ESB) consensus statement.

Rickets, one of the leading causes of bony deformities and short stature, can be calciopenic (inciting event is defective intestinal calcium absorption) or phosphopenic (inciting event is phosphaturia). Early diagnosis and timely treatment of rickets are crucial for correction of the limb deformities. Guidelines exist for nutritional rickets, but the diagnosis and management of the relatively uncommon forms of rickets are complex. This consensus aims to formulate a simplified diagnostic approach for rickets, especially in resource-limited settings. The consensus statement has been formulated by a 29-member committee from the Endocrine Society of Bengal. The process included forming a working group, conducting a literature review, identifying controversies, drafting, and discussion at a consensus meeting. Participants rated their agreement with the clinical practice points, and a 70% consensus was required. Input integration and further review led to the final consensus statements. Children with suspected rickets should initially be examined for distinctive skeletal deformities. The diagnosis of rickets should be confirmed with characteristic radiographic abnormalities. It is advisable to order tests for serum calcium, inorganic phosphorus (Pi), liver function, 25-hydroxyvitamin D (25OHD), parathyroid hormone, creatinine, and potassium in all patients with rickets. In cases of refractory rickets, it is also recommended that assessments be conducted for spot urine calcium, Pi, creatinine, and, blood gas analysis. In children with rickets and metabolic acidosis, tests for glycosuria, uricosuria, aminoaciduria, low molecular weight proteinuria, and albuminuria should be conducted. In children with resistant calciopenic rickets and sufficient serum 25OHD levels, serum 1,25(OH)2D concentration should be tested. 1,25(OH)2 D and fibroblast growth factor 23 estimation is useful for certain forms of phosphopenic rickets.

Maternal loss of 24-hydroxylase causes increased intestinal calcium absorption and hypercalcemia during pregnancy but reduced skeletal resorption during lactation in mice.

Inactivation of 24-hydroxylase (CYP24A1) causes mild hypercalcemia in humans that becomes severe and life-threatening during pregnancy through unclear mechanisms. We studied Cyp24a1 null mice during pregnancy, lactation, and post-weaning. We hypothesized that Cyp24a1 nulls have a much greater increase in calcitriol during pregnancy and lactation, leading to markedly increased intestinal calcium absorption and reduced lactational bone loss. WT and Cyp24a1 null sisters were mated to Cyp24a1+/- males. Timepoints included baseline (BL), late pregnancy (LP), mid-lactation (ML), late lactation (LL), and weekly x4 weeks of post-weaning recovery (R1-4). Assessments included intestinal calcium absorption (IntCaAbs) by gavage of 45Ca, bone mineral content (BMC) by DXA, microCT of femurs, 3-point bending tests of tibias, serum hormones, serum and urine minerals, milk analysis, and intestinal gene expression. At LP, whole body BMC increased equally by ~12% in null and WT. Calcitriol was 2.5-fold higher in nulls vs WT, accompanied by 3-fold increased IntCaAbs, hypercalcemia, hypercalciuria, and 6.5-fold higher FGF23. PTH was suppressed in both. Twenty percent of null dams died during delivery but their serum calcium at LP did not differ from Cyp24a1 nulls that survived. At ML, calcitriol, IntCaAbs, and FGF23 declined in both genotypes but remained higher than BL values in Cyp24a1 nulls. By LL, nulls were still hypercalcemic vs WT, and had lost less mean whole body BMC (11% vs. 21%, P<.02), but by micro-CT there were no differences from WT in cortical or trabecular bone mass. Lactational losses in BMC, cortical thickness, and trabecular number were restored by R4 in both genotypes. In summary, ablation of Cyp24a1 increased IntCaAbs and caused hypercalcemia during pregnancy and lactation, late gestational mortality in some nulls, and reduced lactational BMC loss. Treating women with gestational hypercalcemia from CYP24A1 mutations should focus on reducing calcitriol or IntCaAbs, since increased bone resorption is not the cause.

7293 An Unusual Case Of Adult-Onset Heterozygous HHRH In A Male With Normal Phosphorus And Severe Osteoporosis

Abstract Disclosure: M. El Najjar: None. A. Sabet: None. D. Willard: None. Introduction: Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic disorder characterized by renal phosphate wasting, which can affect bone metabolism. Although onset is typically in childhood, adult-onset forms have been described, and the manifestation depends on the zygosity of each patient. Most commonly, adults with HHRH demonstrate markedly reduced bone density and multiple fractures. Heterozygotes have milder presentations with mild hypophosphatemia, hypercalciuria, and nephrolithiasis, usually without bone disease; however, it is less well characterized. Case report: A 73-year-old man suffered an L1 vertebral compression fracture while playing golf. Bone mineral density testing revealed T-scores of -0.9 at the lumbar spine and -3.4 at the femoral neck (Z-score -2.6). He started alendronate 70 mg weekly for osteoporosis treatment. A year later, the patient sustained an L3 vertebral compression fracture while on treatment with no improvement in his bone density. His family history was remarkable for osteoporosis in his mother but no nephrolithiasis or hypercalcemia. Physical examination was unremarkable. Laboratory evaluation was notable for a 1,25-dihydroxyvitamin D of 87 pg/mL (18-72 pg/mL) , a 24-hour urine calcium of 240 mg/g Cr (30-210 mg/g),a serum PTH of 9 pg/mL (16-77 pg/ml) , but otherwise a normal serum calcium level of 9.4 mg/dL (8.6-10.3 mg/dL) and serum phosphate level of 2.2 mg/dl (2.1-4.3 mg/dl). Genetic testing revealed heterozygosity for SLC34A3 mutation, which is associated with HHRH. The patient discontinued alendronate and started 250 mg phosphorus supplementation 4 times daily. At 6 months follow up, he reported improvement in his body aches, and biochemical testing showed normalization of his 24-hour urine calcium to 171 mg/g Cr and serum PTH to 21 pg/mL. Repeat bone density scan after 1 year of phosphorus supplementation showed T-scores of -0.3 at the lumbar spine (5.8% increase) and -2.6 at the femoral neck (15.5% increase). Clinical Lesson: HHRH is an autosomal recessive hypophosphatemic rickets associated with mutations of the SLC34A3 sodium-phosphate cotransporter, where it is believed that selective phosphate wasting leads to increased calcitriol, in contrast to other forms of hypophosphatemic rickets, causing increased intestinal calcium absorption and resulting hypercalciuria. Adult-onset forms of HHRH have been described in heterozygous carriers of the SLC34A3 mutation and usually present with low to low-normal phosphate levels, hypercalciuria, and nephrolithiasis but without bone disease. However, clinical variations of heterozygous carriers have also been recognized, and therefore are likely underdiagnosed. Our patient’s serum phosphorus level was within the normal range, and hypophosphatemic rickets could have been missed if a more extensive laboratory evaluation had not been performed. Presentation: 6/1/2024

THE EFFECT OF HIGH FLUORIDE INTAKE ON SODIUM, AND POTASSIUM AND CALCIUM LEVELS IN SHEEP BLOOD SERUM

This experiment was carried out to investigate levels of sodium, potassium and calcium in ovine blood serum for 12 weeks during which fluoride (100 ppm) was added to the ration. The rams remained physically in good condition and there were no lesions in the teeth, gums and joints. With the exception of an increase in sodium at the end of the first week, sodium and potassium levels were not influenced. This finding could point out to the possibility of failure of the added fluoride to induce significant changes in kidney and aldosterone functions regarding regulation of these two ions in blood. There was a general tendency of the total calcium level to decrease which reached statistical significance in samples of three weeks. Such decrease could be due to a decline in calcium intestinal absorption and an increase in bone deposition and excretion with urine.

MAPK signaling pathway participates in the regulation of intestinal phosphorus and calcium absorption in broiler chickens via 1,25-dihydroxyvitamin D3

Four experiments were performed to investigate the role of the mitogen-activated protein kinase (MAPK) signaling pathway in intestinal absorption of phosphorus (P) and calcium (Ca) in broiler chickens. Experiment 1 assessed how dietary levels of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) influence the gene expression of intestinal P and Ca transporters in broilers. Experiment 2 evaluated the effects of 1,25(OH)2D3 administered via intraperitoneal injection on the extracellular signal-regulated kinase (ERK) and p38 mitogen-activated protein kinase (p38MAPK) signaling pathways. Experiments 3 and 4 investigated the effect of ERK and p38MAPK inhibitors on the expression of intestinal P and Ca transporters. The findings demonstrated that broilers (1-21 days old) fed a 1,25(OH)2D3-deficient diet (0.625 µg/kg) exhibited reduced body weight, tibia P and Ca levels, and mRNA levels of P transporters (NaPi-IIb, PiT-1, and PiT-2), Ca transporters (NCX1, PMCA1b, and CaBP-D28k), vitamin D receptors (VDR), ERK, and p38MAPK in the duodenum (Experiment 1) (P < 0.05). By comparison, the growth, bone quality, and mRNA levels of genes (except for duodenal NaPi-IIb) in broilers were similar to those in broilers fed the control diet when dietary 1,25(OH)2D3 was adequate (5 µg/kg) (Experiment 1) (P > 0.05). After intraperitoneal injection of 1,25(OH)2D3, the mRNA level of jejunal NaPi-IIb and the protein level of p-p38MAPK/t-p38MAPK in broilers (9-14 days old) decreased (P < 0.05), whereas the mRNA level of CaBP-D28k and the protein level of p-ERK/t-ERK increased (Experiment 2) (P < 0.05). The mRNA and protein expression of jejunal NaPi-IIb and the protein expression of CaBP-D28k in broilers (9-17 days old) treated with the ERK inhibitor PD98059 were greater than those in the control group (Experiment 3) (P < 0.05). Similarly, compared with control broilers, broilers (9-17 days old) treated with the p38MAPK inhibitor SB203580 showed elevated mRNA expression of jejunal NaPi-IIb and CaBP-D28k (Experiment 4) (P < 0.05). These results suggest that adequate supplementation with 1,25(OH)2D3 (5 µg/kg) can restore broiler growth and bone quality by upregulating the transcription of genes involved in intestinal P and Ca absorption. Additionally, the ERK and p38MAPK signaling pathways are implicated in the modulatory effect of 1,25(OH)2D3 on the absorption of P and Ca in broilers.

Nutrition, Vitamin D, and Calcium in Elderly Patients before and after a Hip Fracture and Their Impact on the Musculoskeletal System: A Narrative Review.

Hip fractures are a major health issue considerably impacting patients' quality of life and well-being. This is particularly evident in elderly subjects, in which the decline in bone and muscle mass coexists and predisposes individuals to fall and fracture. Among interventions to be implemented in hip fractured patients, the assessment and management of nutritional status is pivotal, particularly in subjects older than 65. Nutrition plays a central role in both primary and secondary preventions of fracture. An adequate protein intake improves muscle mass and strength and the intestinal absorption of calcium. Other nutrients with recognized beneficial effects on bone health are calcium, vitamins D, K, and C, potassium, magnesium, folate, and carotenoids. With reference to calcium, results from longitudinal studies showed that the consumption of dairy foods has a protective role against fractures. Moreover, the most recent systematic reviews and meta-analyses and one umbrella review demonstrated that the combination of calcium and vitamin D supplementation significantly reduces hip fracture risk, with presumed higher efficacy in older and institutionalized subjects. Owing to these reasons, the adequate intake of calcium, vitamin D, protein, and other macro and micronutrients has been successfully implemented in the Fracture Liaison Services (FLSs) that represent the most reliable model of management for hip fracture patients. In this narrative review, papers (randomized controlled trials, prospective and intervention studies, and systematic reviews) retrieved by records from three different databases (PubMed, Embase, and Medline) have been analyzed, and the available information on the screening, assessment, and management of nutritional and vitamin D status and calcium intake in patients with hip fractures is presented along with specific prevention and treatment measures.

Significance of Duodenal Prolactin Receptor Modulation by Calcium and Vitamin D in Sulpiride-Induced Hyperprolactinemia.

Background and Objectives: Hyperprolactinemia, as a potential side-effect of some antipsychotic medications, is associated with decreased bone density and an increased risk of fractures. This study investigates whether calcium and vitamin D supplementation affects prolactin receptor (Prlr) gene expression in the duodenum, vertebrae, and kidneys of female rats with sulpiride-induced hyperprolactinemia. Materials and Methods: Twenty-one-week-old female Wistar rats were assigned to three groups: Group S consisted of ten rats who received sulpiride injections (10 mg/kg) twice daily for 6 weeks; Group D (10 rats) received daily supplementation of 50 mg calcium and 500 IU vitamin D along with sulpiride for the last 3 weeks; and Group C consisting of seven age-matched nulliparous rats serving as a control group. Real-time PCR was used to assess Prlr gene expression in the duodenum, vertebrae, and kidneys. Results: In Group S, Prlr gene expression was notably decreased in the duodenum (p < 0.01) but elevated in the vertebrae and kidneys compared to Group C. Conversely, Group D exhibited significantly increased Prlr expression in the duodenum (p < 0.01) alongside elevated expression in the vertebrae and kidneys. Conclusions: In sulpiride-induced hyperprolactinemia, decreased Prlr gene expression in the duodenum may lead to reduced intestinal calcium absorption. Consequently, prolactin may draw calcium from the skeletal system to maintain calcium balance, facilitated by increased Prlr gene expression in the vertebrae. However, vitamin D supplementation in sulpiride-induced hyperprolactinemia notably enhances Prlr gene expression in the duodenum, potentially ameliorating intestinal calcium absorption and mitigating adverse effects on bone health.

Endoplasmic reticulum protein of 57 kDa sulfhydration promotes intestinal calcium absorption to attenuate primary osteoporosis

Endogenous hydrogen sulfide (H2S) plays an important role in bone metabolism. However, the exact role of H2S in intestinal calcium and phosphorus absorption and its potential in preventing and treating primary osteoporosis remains unknown. Therefore, this study aimed to investigate the potential of H2S in promoting intestinal calcium and phosphorus absorption and alleviating primary osteoporosis. We measured the apparent absorptivity of calcium, femoral bone density, expression and sulfhydration of the duodenal endoplasmic reticulum protein of 57 kDa (ERp57), duodenal cystathionine γ-lyase (CSE) expression, and serum H2S content in adult and old CSE-knockout and wild-type mice. We also assessed intracellular reactive oxygen species (ROS) and Ca2+ content in CSE-overexpressing or knockout intestinal epithelial cell (IEC)-6 cells. In senile mice, CSE knockout decreased endogenous H2S, ERp57 sulfhydration, and intestinal calcium absorption and worsened osteoporosis, which were partially reversed by GYY4137, an H2S donor. CSE overexpression in IEC-6 cells increased ERp57 sulfhydration, protein kinase A and C activity, and intracellular Ca2+, whereas CSE knockout exerted the opposite effects. Furthermore, hydrogen peroxide (H2O2) stimulation had similar effects as in CSE knockout, which were reversed by pretreatment with sodium hydrosulfide before H2O2 stimulation and restored by DL-dithiothreitol. These findings suggest that H2S attenuates primary osteoporosis by preventing ROS-induced ERp57 damage in intestinal epithelial cells by enhancing ERp57 activity and promoting intestinal calcium absorption, thereby aiding in developing therapeutic interventions to prevent osteoporosis.

Physiology of Vitamin D-Focusing on Disease Prevention.

Vitamin D is a crucial micronutrient, critical to human health, and influences many physiological processes. Oral and skin-derived vitamin D is hydroxylated to form calcifediol (25(OH)D) in the liver, then to 1,25(OH)2D (calcitriol) in the kidney. Alongside the parathyroid hormone, calcitriol regulates neuro-musculoskeletal activities by tightly controlling blood-ionized calcium concentrations through intestinal calcium absorption, renal tubular reabsorption, and skeletal mineralization. Beyond its classical roles, evidence underscores the impact of vitamin D on the prevention and reduction of the severity of diverse conditions such as cardiovascular and metabolic diseases, autoimmune disorders, infection, and cancer. Peripheral target cells, like immune cells, obtain vitamin D and 25(OH)D through concentration-dependent diffusion from the circulation. Calcitriol is synthesized intracellularly in these cells from these precursors, which is crucial for their protective physiological actions. Its deficiency exacerbates inflammation, oxidative stress, and increased susceptibility to metabolic disorders and infections; deficiency also causes premature deaths. Thus, maintaining optimal serum levels above 40 ng/mL is vital for health and disease prevention. However, achieving it requires several times more than the government's recommended vitamin D doses. Despite extensive published research, recommended daily intake and therapeutic serum 25(OH)D concentrations have lagged and are outdated, preventing people from benefiting. Evidence suggests that maintaining the 25(OH)D concentrations above 40 ng/mL with a range of 40-80 ng/mL in the population is optimal for disease prevention and reducing morbidities and mortality without adverse effects. The recommendation for individuals is to maintain serum 25(OH)D concentrations above 50 ng/mL (125 nmol/L) for optimal clinical outcomes. Insights from metabolomics, transcriptomics, and epigenetics offer promise for better clinical outcomes from vitamin D sufficiency. Given its broader positive impact on human health with minimal cost and little adverse effects, proactively integrating vitamin D assessment and supplementation into clinical practice promises significant benefits, including reduced healthcare costs. This review synthesized recent novel findings related to the physiology of vitamin D that have significant implications for disease prevention.

#1834 Prevalence of nephrolithiasis in patients with idiopathic hypercalciuria after two decades of follow-up

Abstract Background and Aims Idiopathic hypercalciuria (IH) is the main metabolic abnormality that causes kidney stones. It is linked to high intestinal calcium absorption and osteopenia. However, not all patients diagnosed with IH develop kidney stones. In this study, we examined a cohort of patients diagnosed of IH during childhood to determine the prevalence of lithiasis in adulthood. Method Longitudinal study that evaluated the prevalence of lithiasis in 35 patients (12 female, 23 male) diagnosed of IH during childhood (mean age of 7.7 ± 3 years). The patients were followed until adulthood (mean age 28.2 ± 3.1 years) with a median follow-up of 18.2 years (IQR: 12.2-19.3). IH diagnosis was made by urinary calcium excretion higher than 4 mg/Kg/day in two consecutive samples. In both periods, clinical and demographic data were collected, including urinalysis and urinary ratios (calcium/creatinine, calcium/citrate, oxalate/creatinine, and citrate/creatinine) in an isolated sample of the first morning urine, as well as the performance of renovesical ultrasound. Results In pediatric age, 8 patients (26%) presented nephrolithiasis on ultrasound, and 14 (43.8%) in adulthood, 6 of them experiencing episodes of nephritic colic. During the study, we observed a decrease in urinary calcium excretion, as expressed by the calcium/creatinine ratio (adult age 0.16 ± 0.9 mg/dl vs. childhood 0.28 ± 0.1 mg/dl, p = 0.000), and an hypocitraturia increase (citrate/creatinine ratio in childhood 887 ± 349 mg/dl and in adulthood 357.7 ± 363 mg/dl, p = 0.000). A decreased citrate/creatinine ratio in adulthood was associated with nephrolithiasis (p &amp;lt; 0.007). Only 4 patients (50%) had nephrolithiasis at both ages. Conclusion These results suggest that hypercalciuria tends to correct spontaneously in adulthood, and although the prevalence of nephrolithiasis increased, it is more related to hypocitraturia.

Role of intestinal claudin-2 in calcium transport and kidney stone disease

Background: Kidney stone disease is characterized by intestinal hyperabsorption of calcium and hypercalciuria, leading to the formation of calcium crystals in the kidney. Claudin-2 is a tight junction protein that forms paracellular cation pores and mutations in its gene are associated with kidney stone disease. We have recently shown that mice deficient in Cldn2 are hypercalciuric due to both decreased renal reabsorption and increased intestinal absorption of calcium and develop medullary mineral deposits reminiscent of kidney stone formers. We, therefore, hypothesized that intestinal claudin-2 is important for calcium secretion, especially in the colon, and that loss of claudin-2 results in increased net intestinal calcium absorption, thereby contributing to kidney stone disease. Method: Villin-Cre (Vil1-Cre/1000Gum) mice were crossed to Cldn2 floxed mice to generate intestine-specific claudin-2 knockout mice. Successful knockout of claudin-2 was confirmed at the mRNA and protein level using qPCR, immunofluorescence staining, and western blot. Male and female littermates were characterized for hypercalciuria from age 3-10 weeks. Circulating levels of parathyroid hormone and 1,25-dihydroxyvitamin D (1,25(OH)2D) were measured by ELISA, and mRNA levels of seven paracellular and transcellular calcium transport genes in the ileum, cecum, distal colon, and nine in the kidney assessed by qPCR. Result: In females, Cldn2 expression was knocked out in the intestine but not in the kidney. However, in males, Cldn2 was knocked out in the intestine and also partially knocked out in the kidneys (where villin is also expressed). Knockout females had normal urine calcium, but knockout males had significantly higher urine calcium at weaning (3 weeks of age) compared to wildtype, which was normalized by 4 weeks of age. At 4 weeks, Cldn19 mRNA was downregulated in knockout mice of both sexes. Male knockout mice had a reduction in intestinal Cldn12, Cldn15, Slc8a1, and increased intestinal Cacnad1, increased renal Cyp27b1 expression, and increased circulating 1,25(OH)2D. Conclusion: Our results suggest that intestine-specific loss of claudin-2, which was only observed in villin-Cre, Cldn2 floxed females, does not cause hypercalciuria. Ongoing whole-body calcium balance and everted sac calcium permeability experiments will determine whether this is because intestinal calcium hyperabsorption is masked by compensatory mechanisms. NIH. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Complex clinical encounter series: osteoporosis presenting during pregnancy and lactation: wait and reassess.

Two months after her first pregnancy, a 35-yr-old exclusively breastfeeding woman bent to move her baby in the car seat and experienced sudden, severe pain from 5 spontaneous vertebral compression fractures. Genomic screen was negative but she had mild ankylosing spondylitis previously well controlled on etanercept. She was vegetarian with a high phytate intake. A lactation consultant had advised her to pump and discard milk between feeds, leading her to believe she produced twice as much milk as her baby ingested. She presented with a LS Z score of -3.6 and a TH Z score of -1.6. After 6 mo postweaning, she was treated with teriparatide (14 mo intermittently over 18 mo) and ultimately achieved a 50% increase in LS bone density and an 8% increase in TH bone density. Her fragility is explained by normal lactational bone loss amplified by excessive milk production and phytate-induced impairment of intestinal calcium absorption, ankylosing spondylitis, and the bend-and-lift maneuver. The marked increase in bone density resulted from the combined effects of spontaneous recovery and pharmacotherapy. Spontaneous recovery of bone mass and strength should occur during 12 mo after weaning in all women, including those who have fractured.

Structural characterization and calcium absorption-promoting effect of sucrose-calcium chelate in Caco-2 monolayer cells and mice.

Sucrose emerges as a chelating agent to form a stable sucrose-metal-ion chelate that can potentially improve metal-ion absorption. This study aimed to analyze the structure of sucrose-calcium chelate and its potential to promote calcium absorption in both Caco-2 monolayer cells and mice. The characterization results showed that calcium ions mainly chelated with hydroxyl groups in sucrose to produce sucrose-calcium chelate, altering the crystal structure of sucrose (forming polymer particles) and improving its thermal stability. Sucrose-calcium chelate dose dependently increased the amount of calcium uptake, retention, and transport in the Caco-2 monolayer cell model. Compared to CaCl2 , there was a significant improvement in the proportion of absorbed calcium utilized for transport but not retention (93.13±1.75% vs. 67.67±7.55%). Further treatment of calcium channel inhibitors demonstrated the active transport of sucrose-calcium chelate through Cav1.3. Cellular thermal shift assay and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays indicated that the ability of sucrose-calcium chelate to promote calcium transport was attributed to its superior ability to bind with PMCA1b, a calcium transporter located on the basement membrane, and stimulate its gene expression compared to CaCl2 . Pharmacokinetic analysis of mice confirmed the calcium absorption-promoting effect of sucrose-calcium chelate, as evident by the higher serum calcium level (44.12±1.90mg/L vs. 37.42±1.88mmol/L) and intestinal PMCA1b gene expression than CaCl2 . These findings offer a new understanding of how sucrose-calcium chelate enhances intestinal calcium absorption and could be used as an ingredient in functional foods to treat calcium deficiency. PRACTICAL APPLICATION: The development of high-quality calcium supplements is crucial for addressing the various adverse symptoms associated with calcium deficiency. This study aimed to prepare a sucrose-calcium chelate and analyze its structure, as well as its potential to enhance calcium absorption in Caco-2 monolayer cells and mice. The results demonstrated that the sucrose-calcium chelate effectively promoted calcium absorption. Notably, its ability to enhance calcium transport was linked to its strong binding with PMCA1b, a calcium transporter located on the basement membrane, and its capacity to stimulate PMCA1b gene expression. These findings contribute to a deeper understanding of how the sucrose-calcium chelate enhances intestinal calcium absorption and suggest its potential use as an ingredient in functional foods for treating calcium deficiency.

P-12 Postpartum vertebral compressive fractures in a young female with osteoporosis - A case report

Abstract Introduction Osteoporosis is а metabolic disorder characterized by low bone mass and deep changes in bone architecture that lead to an increased vertebral or hip fracture in elderly. Osteoporosis in young population is a very rare condition especially when is associated with compressive fractures. Pregnancy and postpartum-related osteoporosis is condition that occurs in the last trimester of pregnancy оr in the first months of lactation. It is self-limited condition that return to normal after 12-18 months. In rare cases leаds to spinal compressive fractures. Clinical Case We present a 33-year-old female with back pain that occurs after birth during the early lactation period. In consultation with an orthopedic surgeon, an X-ray was made on the thoracolumbar spinal column with a finding of vertebral compressive fractures. A DEXA scan (double energy-X rays of absorptiometry) is also made with the finding of vertebral osteoporosis and hip osteopenia. We calculate BMI and perform blood tests for vitamin D3, calcium, hormones and markers for bone metabolism. This was our patient's first birth, she was thin with height 157 cm, weight 42 kg and calculated BMI-17. Blood test showed very low concentration of vitamin D3- 16 ng/ml (20-44) with normal level of calcium- 1,20 mmol/l (1,10-1,40) and PTH-31,01 pg./ml (15-65). Thyroid, gonadal and adrenal axis was with normal function. We told the patient to stop the lactation and to take a supplementation of vitamin D3 2000 IE, Calcium 1000 mg and bisphosphonates (alendronate). After two years of treatment, we made a control DEXA scan. Our patient now has vertebral osteopenia, normal serum concentration of vitamin D (44 ng/ml) and her weight is 48 kg. She feels good, has no pain and no new fractures. Conclusion Pregnancy and lactation increase need for calcium and this condition is complemented by increased intestinal absorption of calcium and increased bone resorption of the mother's skeleton. Risk factors for low bone density are deficit of 1-25 OH vitamin D3, malnutrition, low body mass index, treatment with low dose of enoxaparin (LMWH), physical inactivity. Our patient has an increased risk of low bone density (she has a low body mass index, low serum concentration of 1–25 OH vitamin D3 and this was her first pregnancy). Normal serum level 1–25 OH vitamin D concentration is required to establish calcium metabolism and prevent low bone density, osteopenia or osteoporosis. Antiresorptive therapy with bisphosphonates lead to rapid improvement in bone density, prevent new fractures and relieves pain. Treatment of postpartum osteoporosis is debatable because this condition is reversible, so when we decide to treat or not to treat, we must consider present of fractures, pain and plan for future pregnancy.

Alteration in the gut microbiome is associated with changes in bone metabolism after laparoscopic sleeve gastrectomy.

Laparoscopic sleeve gastrectomy (LSG), the most common bariatric surgical procedure, leads to durable weight loss and improves obesity-related comorbidities. However, it induces abnormalities in bone metabolism. One unexplored potential contributor is the gut microbiome, which influences bone metabolism and is altered after surgery. We characterized the relationship between the gut microbiome and skeletal health in severe obesity and after LSG. In a prospective cohort study, 23 adults with severe obesity underwent skeletal health assessment and stool collection preoperatively and 6mo after LSG. Gut microbial diversity and composition were characterized using 16S rRNA gene sequencing, and fecal concentrations of short-chain fatty acids (SCFA) were measured with LC-MS/MS. Spearman's correlations and PERMANOVA analyses were applied to assess relationships between the gut microbiome and bone health measures including serum bone turnover markers (C-terminal telopeptide of type 1 collagen [CTx] and procollagen type 1N-terminal propeptide [P1NP]), areal BMD, intestinal calcium absorption, and calciotropic hormones. Six months after LSG, CTx and P1NP increased (by median 188% and 61%, P< .01) and femoral neck BMD decreased (mean -3.3%, P< .01). Concurrently, there was a decrease in relative abundance of the phylum Firmicutes. Although there were no change in overall microbial diversity or fecal SCFA concentrations after LSG, those with greater within-subject change in gut community microbial composition (β-diversity) postoperatively had greater increases in P1NP level (ρ= 0.48, P= .02) and greater bone loss at the femoral neck (ρ= -0.43, P= .04). In addition, within-participant shifts in microbial richness/evenness (α-diversity) were associated with changes in IGF-1 levels (ρ= 0.56, P< .01). The lower the postoperative fecal butyrate concentration, the lower the IGF-1 level (ρ= 0.43, P= .04). Meanwhile, the larger the decrease in butyrate concentration, the higher the postoperative CTx (ρ= -0.43, P= .04). These findings suggest that LSG-induced gut microbiome alteration may influence skeletal outcomes postoperatively, and microbial influences on butyrate formation and IGF-1 are possible mechanisms.

Vitamin D3 deficiency and coronavirus-related health problems

Introduction: In addition to boosting calcium absorption in the small intestine and preserving sufficient levels of calcium and phosphate in the serum to support proper bone mineralization, Vitamin D3 fortifies the immune system. Vitamin D3 deficiency can occur when regular intakes are gradually below recommended levels and when people get little sunshine exposure. Materials and Methods: The study was conducted using a case series study approach. A structured checklist was utilized on 107 individuals who had recovered from corona disease to identify the causes behind the unfavorable health effects they continue to experience. In addition, the patients underwent extensive laboratory blood testing in a specialized laboratory and received follow-up care for a period of 6 months. The results were analyzed using the Chi-square test and the Paired t-test using the SPSS software. Results: Despite the finding that 84.1% of the study group had Vitamin D3 levels below the normal range, their physical health conditions had considerably improved as a result of the treatment they received. Conclusion: The study found that patients with coronavirus infection had a high prevalence of Vitamin D3 deficiency. After 6 months, this percentage dropped considerably, raising the possibility that the coronavirus may have contributed to the drop in plasma Vitamin D3 levels. To find out how long-lasting COVID-19 symptoms are related to Vitamin D3 deficiency, more research is required. The following core competencies are addressed in this article: Medical knowledge, Patient care and procedural skills.

The complex relationship between vitamin D and kidney stones: balance, risks, and prevention strategies.

The association between vitamin D and kidney stones is characterized by a remarkable multi-dimensional complexity involving numerous physiological and metabolic pathways. Vitamin D is pivotal in maintaining calcium-phosphorus metabolic homeostasis and bone health. However, fluctuations in its intake, whether excessive or insufficient, May potentially increase the risk of kidney stones. Vitamin D exerts its influence on kidney stone formation indirectly by increasing the efficiency of intestinal calcium absorption and regulating renal calcium excretion. Moreover, there is a robust correlation between various states of vitamin D, particularly its active form, 1,25-dihydroxyvitamin D, and the development of numerous kidney stones. This finding underscores the necessity of individualized medical treatment in vitamin D supplementation and kidney stone prevention. When developing treatment strategies, it is essential to consider the patient's genetic background, lifestyle, environmental factors, and overall health. To prevent the formation of kidney stones, it is recommended that patients adopt a comprehensive approach, which May include measures such as moderate sun exposure, dietary modification, moderate exercise, and weight management. These preventive measures are designed to maintain healthy calcium and phosphorus metabolism and reduce kidney stone formation risk. Future studies should aim to elucidate the detailed mechanisms of vitamin D metabolism, individual differences, and the role of genes in this process. Furthermore, the role of lifestyle interventions in preventing kidney stones requires greater attention. Moreover, the implementation of large-scale, long-term prospective studies and randomized controlled trials will facilitate the assessment of the actual effects of diverse vitamin D supplementation strategies, thereby providing a robust scientific foundation for advancing more precise prevention strategies and clinical guidelines.

Pectin Modulates Calcium Absorption in Polarized Caco-2 Cells via a Pathway Distinct from Vitamin D Stimulation.

Pectin, a type of soluble fiber, promotes morphological changes in the small intestinal villi. Although its physiological significance is unknown, we hypothesized that changes in villus morphology enhance the efficiency of nutrient absorption in the small intestine and investigated the effect of pectin derived from persimmon on calcium absorption using polarized Caco-2 cells. In polarized Caco-2 cells, pectin altered the mRNA expression levels of substances involved in calcium absorption and the regulation of intracellular calcium concentration and significantly reduced calcium absorption. Although this was comparable to the results of absorption and permeability associated with the addition of active vitamin D, the simultaneous action of pectin and active vitamin D did not show any additive effects. Furthermore, as active vitamin D significantly increases the activity of intestinal alkaline phosphatase (ALP), which is known to be involved in the regulation of intestinal absorption of calcium and lipids, we also investigated the effect of pectin on intestinal ALP activity. As a result, it was found that, unlike the effect of active vitamin D, pectin significantly reduced intestinal ALP activity. These results suggest that pectin stimulates polarized Caco-2 cells through a mechanism distinct from the regulation of calcium absorption by vitamin D, modulating total calcium absorption from the elongated villi through morphological changes in the small intestine by suppressing it at the cellular level.

Influential Factors in Intestinal Absorption and Renal Reabsorption of Calcium

Calcium is one of the vital and essential elements in the body, serving as a primary constituent of bones and teeth. It plays a fundamental role in nerve signal transmission, muscle contractions, heart rate regulation, blood clotting, energy production, glandular secretion, and immune system maintenance. Calcium is abundantly found in dietary sources, with most of it residing in the teeth and bones within the body. Approximately 40% of daily dietary calcium is absorbed primarily at the beginning of the intestine and before gastric juice neutralization, while 60% of it is excreted through feces. Calcium absorption occurs in two forms, passive and active, through the intestines, and renal reabsorption takes place through the kidneys. Various factors such as intestinal environment, dietary components (including lactose, proteins, and amino acids),bile salts, parathyroid hormone, vitamin D, acidic pH, health status, age, and growth hormone influence intestinal calcium absorption positively. Conversely, fatty acids, phytic acid, aging, alkaline pH, iron, magnesium, calcitonin hormones, and glucocorticoids reduce calcium absorption. Parathyroid hormone, calcitonin hormone, vitamin D, and dietary regimen significantly contribute to the active reabsorption of calcium through renal tubules. Despite the considerable variations in the calcium content of dietary sources, a highly precise regulatory system controls vitamin D production, preventing fluctuations in plasma calcium ion concentrations. This regulation helps prevent hypocalcemia and hypercalcemia, which can lead to numerous irregularities in the body.